Study On The Effect And Mechanisms About Coleus Forskohlii In Relieving Asthma Symptoms

Bronchial asthma is a chronic respiratory disease that has threatened human health seriously.It is mainly characterized by airway inflammatory infiltration,airway remodeling and airway hyperreactivity.Tissue injury caused by airway inflammation can aggravate asthma.In addition,airway remodeling is mainly manifest as poor reversible or irreversible airway ventilation disorder and airway hyperreactivity.This is an important cause of incurable asthma.At present,there are many kinds of drugs used to treat asthma in clinic,but they have different degrees of side effects.Therefore,it is significant to develop an asthma drug with evident efficacy and small side effects.Coleus forskohlii is an herb commonly used to treat cough and asthma among the civilian population.There is also “capsule of Coleus forskohlii” developed by using Coleus forskohlii as principle drug in the market.Coleus forskohlii has remarkable effect in treating asthma,however the exact mechanism involved is not clear.This research explored the anti-asthma mechanism of extract of Coleus forskohlii(ECFK)by using modern pharmacology and molecular biology.Objective: To investigating the mechanism of ECFK in relieving asthma for providing scientific basis of applying Coleus forskohlii to anti-asthma in clinic.At the same time,it aims to provide a foundation for the further development of anti-asthma innovative drugs.Method: Diacolation method was applied to obtain ECFK,guinea pigs were administered with ECFK for three days.Then they were induced by a spray of phosphoric acid histamine,the asthma incubation period of guinea pigs was recorded and analyzed.Rats were sensitized by OVA combined with aluminium hydroxide to construct the asthma model.Then they were administrated with ECFK.H&E were used to evaluate pathological changes in lung tissue.ELISA was used to determine change of some cytokines from Th1,Th2,Th17 content in serum and BALF.Immunohistochemistry was used to detect the expression of MMP-9 and TIMP-1 related to degradation and deposition of ECM.Western blot analysis was used to assess the expression of specific transcription factors T-bet,GATA-3,ROR-?t of Th1,Th2,Th17,and analyze the expression of ICAM-1,p-p65,?-SMA,MMP-9,TIMP-1 and MAPK pathway related proteins participating in inflammation and airway remodeling.Result: Compared with the histamine phosphate group,the asthma incubation period of guinea pigs in the 6.4 g/kg and 12.8 g/kg ECFK groups were significantly prolonged,the differences were statistically significant(p<0.01).The H&E results showed that severe pathological injury of lung tissue occurred in OVA group compared to the control group,pathological damage of lung in the 6.4 g/kg and 12.8 g/kg ECFK groups were significantly lower when compared to that in the OVA group.Moreover,ELISA results demonstrated that IL-4,IL-5,and IL-17 A content of OVA group in serum and BALF were significantly increased(p<0.01),and IFN-?,IL-10 were decreased compared with control group(p<0.05,p<0.01).IL-4,IL-5,and IL-17 A of 6.4g/kg and 12.8 g/kg ECFK groups in serum and BALF were significantly decreased,IFN-? and IL-10 were increased remarkably compared to OVAgroup(p<0.05,p<0.01).Immunohistochemical results showed that positive expression of MMP-9 and TIMP-1 were significantly increased in OVA group compared with control group.Positive expression were signally decreased in6.4 g/kg and 12.8 g/kg ECFK groups,the expression levels of TIMP-1 in 6.4g/kg and 12.8 g/kg ECFK groups were even similar with control group.In addition,the result of WB indicated that the GATA-3,ROR-?t,ICAM-1,p-p65,?-SMA,MMP-9,TIMP-1,p-ERK,p-JNK and p-p38 in OVA group were significantly increased compared to control group(p<0.05,p<0.01).ECFK treatment resulted in down-regulation of these proteins in lung tissue after being sensitized by OVA.Specific transcription factor T-bet of Th1 in OVA group was significantly decreased compared to control group,the level of T-bet increased after ECFK treatment,these differences were statistically significant(p<0.05,p<0.01).Conclusion: In conclusion,our findings indicated that ECFK could effectively prolong the asthma incubation period of guinea pigs to exert the pharmacological effect of relieving cough and asthma.It regulated cytokines and the expression of specific transcription factor of Th1,Th2 and Th17 to maintain the balance between the three cells,thereby alleviating inflammatory pathologic injury of OVA induced-asthma.This study also found that ECFK mitigated asthma inflammation and airway remodeling by down-regulating the expression of proteins taking part in ECM degradation and deposition.ECFK treated bronchial asthma effectively further by regulating the expression of related proteins in the MAPK pathway.In conclusion,this study preliminarily interpreted the mechanism of ECFK relieving asthma.It laid a theoretical foundation for clinical use of Coleus forskohlii and the development of innovative asthma drugs by using this herb.